Emerging Roles of SIRT1 in Cancer Drug Resistance.
Emerging Roles of SIRT1 in Cancer Drug Resistance.
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DOI：
10.1177/1947601912473826
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Chen, Wenyong
中科院分区：
文献类型：
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作者：
Wang, Zhiqiang;Chen, Wenyong
对各种治疗干预措施的先天抵抗是癌症的一个标志。近年来，获得性耐药已成为癌症靶向治疗面临的严峻挑战，它使原本成功的靶向药物失去了功效。癌细胞通过原发性和转移性癌症中的多种机制获得抵抗特性，涉及细胞内在和外在因素。越来越多的证据表明，哺乳动物应激反应基因 Sirtuin 1 (SIRT1) 在癌症耐药性的多个方面发挥着关键作用。 SIRT1减少药物渗透，赋予癌细胞增殖和抗凋亡生存优势，通过基因突变促进获得性耐药，促进癌症干细胞的存活，并以细胞自主和非自主方式改变肿瘤微环境以实现耐药。本文概述了 SIRT1 在癌症耐药性中的作用的研究进展，并强调了以 SIRT1 为靶点作为克服癌症耐药性和改善治疗结果的新策略的前景。
Innate resistance to various therapeutic interventions is a hallmark of cancer. In recent years, acquired resistance has emerged as a daunting challenge to targeted cancer therapy, which abolishes the efficacy of otherwise successful targeting drugs. Cancer cells gain the resistance property through a variety of mechanisms in primary and metastatic cancers, involving cellular intrinsic and extrinsic factors. Increasing evidence suggests that the mammalian stress response gene sirtuin 1 (SIRT1) plays a critical role in multiple aspects of cancer drug resistance. SIRT1 decreases drug penetration, confers proliferation and antiapoptotic survival advantages to cancer cells, facilitates acquired resistance through genetic mutations, promotes the survival of cancer stem cells, and changes the tumor microenvironment for resistance in cell-autonomous and -nonautonomous manners. This article provides an overview of research advances in the roles of SIRT1 in cancer drug resistance and highlights the prospect of targeting SIRT1 as a new strategy to overcome cancer drug resistance and improve therapeutic outcomes.